Académique Documents
Professionnel Documents
Culture Documents
Department of
Obstetrics and
Gynaecology,
University Hospital
of Ioannina, 45500
Ioannina, Greece
Alexandros
Sotiriadis
resident in obstetrics
and gynaecology
George
Makrydimas
assistant professor of
obstetrics and
gynaecology
Delvinaki Health
Centre, Delvinaki,
Ioannina, Greece
Stefania
Papatheodorou
rural practitioner
Correspondence to:
A Sotiriadis
asotir@cc.uoi.gr
BMJ 2004;329:1525
152
Summary points
One in five pregnancies is complicated by vaginal
bleeding before 20 weeks gestation
A large empty gestational sac, discrepancy
between gestational age and crown to rump
length, fetal bradycardia or absence of fetal heart
activity at presentation, advanced maternal age,
history of recurrent pregnancy loss, a maternal
serum progesterone < 45 nmol/l or low maternal
serum hCG or inhibin A are adverse prognostic
factors
Fetal heart activity and lack of adverse prognostic
factors conveys a favourable prognosis
Although bed rest and progesterone supplements
are often advised, little evidence supports their
effectiveness
Give anti-Rh D immune globulin to
non-sensitised women with symptoms near, at, or
after 12 gestational weeks
17 JULY 2004
bmj.com
Clinical review
Management
Doctors often prescribe bed rest and progesterone for
women with symptoms of threatened miscarriage, but
evidence is sparse and of low level (table 2).
History
Advancing gestational age1*
Sonography
17 JULY 2004
bmj.com
Fetal bradycardia1*
Discrepancy between gestational age and crown to
rump length4 12
Empty gestational sac >15-17 mm5
153
Clinical review
Bed rest
In one study, 1228 out of 1279 (96%) general
practitioners prescribed bed rest for heavy bleeding in
early pregnancy, although only an eighth of them felt it
was mandatory, and only one third felt it could affect
outcome.3 Only one randomised controlled trial
considers the impact of bed rest on the course of
threatened miscarriage22; 61 women with viable
pregnancies at less than eight gestational weeks and
vaginal bleeding were randomly allocated into either
injections of hCG, injections of placebo, or bed rest.
The abortion rates in the three groups were 30%, 48%,
and 75%significant differences between hCG and
bed rest groups but not between hCG and placebo
groups or between placebo and bed rest groups.
Although hCG performed significantly better than bed
rest in this study, the lack of profound benefit over placebo, the concern about potential development of
ovarian hyperstimulation syndrome, and the fact that
threatened miscarriage may be the result of various
conditions, irrelevant to luteal function, prevented further testing and application of hCG treatment in general obstetric practice.
In a retrospective study of 226 women who were
hospitalised for reasons related to their pregnancy and
previous threatened miscarriage, 16% of 146 women
who were bed resting eventually miscarried, compared
with a fifth of women who did not follow this option
(not significant; P = 0.41).23 In contrast, a recent observational cohort study of 230 women with threatened
miscarriage who were recommended bed rest showed
that women who adhered to this suggestion had a miscarriage rate of 9.9%, compared with 23.3% of women
who continued their usual activities (P = 0.03).24 The
duration of vaginal bleeding, haematoma size and gestational age at diagnosis did not influence miscarriage
rate. Although there is no definite evidence that bed
rest can affect the course of pregnancy, abstinence
from active environment for a couple of days may help
women feel safer,w10 thus providing emotional relief.
Progesterone
Progesterone is prescribed in 13-40% of women
with threatened miscarriage, according to published
series.3 w2 Progesterone is the main product of the
corpus luteum, and giving progestogen is expected to
support a potentially deficient corpus luteum gravi-
Sonography at
presentation
Controls
P value
Mollerw11
Randomised controlled
trial
260
No
Medroxyprogesterone
(three regimens)
60/123
71/137
0.62
Tognoniw12
Randomised controlled
trial
145
No
Hydroxyprogesterone
caproate
49/74
50/71
0.58
Berlew13
Randomised controlled
trial
300
No
Hydroxyprogesterone
caproate
96/154
100/146
0.26
Gerhard
Randomised controlled
trial
52
Yes
Progesterone
23/26
21/26
0.44
Soltanw16
Randomised controlled
trial
35
Yes
Buphenine
19/23
4/12
<0.01
Harrison22
Randomised controlled
trial
61
Yes
hCG
14/20
11/21
0.24
22
Randomised controlled
trial
61
Yes
Bed rest
5/20
11/21
0.07
First author
w14
Harrison
Giobbe23
Ben-Haroush24
154
Intervention
Intervention
group
Retrospective
226
Yes
Bed rest
123/146
64/80
0.41
Prospective observational
230
Yes
Bed rest
180/200
23/30
0.03
17 JULY 2004
bmj.com
Clinical review
3
4
10
11
12
Conclusions
Threatened miscarriage occurs often and is a serious
emotional burden for women. Sonographic evaluation
at presentation can usually differentiate between
intrauterine and extrauterine pregnancy and offer
some prognostic clues. Demonstration of fetal heart
activity is generally associated with a successful
pregnancy rate of 85-97%,4 79 w6 whereas an empty
large gestational sac or a discrepancy between
menstrual and sonographic age of more than a week
indicates a poor prognosis.46 12 Advanced maternal age
and increasing number of previous miscarriages deteriorates prognosis.1 4 w4
Serum hCG, progesterone, inhibin A, and CA125
concentrations may be helpful as predictors; however,
these tests may not be useful in primary care settings.
Although many women with threatened miscarriage are given progestogens and are prescribed bed
rest, little evidence supports these policies. There are
only four old randomised controlled trials on
progestogens,w11-w14 and their cumulative results show
that they do not improve outcome. Data on bed rest are
of even lower quality, as there is only one small
randomised controlled trial,22 one observational,24 and
one retrospective study,23 yielding conflicting results.
Although no evidence based suggestions can be made,
short term abstinence from usual activity may be feasible for women if it is likely to relieve their stress.
Rhesus sensitisation is rare after first trimester
threatened miscarriage; however, consensus suggests
that anti-D immune globulin should be given in cases
BMJ VOLUME 329
17 JULY 2004
bmj.com
13
14
15
16
17
18
19
20
21
22
23
24
25
Makrydimas G, Sebire NJ, Lolis D, Vlassis N, Nicolaides KH. Fetal loss following ultrasound diagnosis of a live fetus at 6-10 weeks of gestation.
Ultrasound Obstet Gynecol 2003;22:368-72.
Johns J, Hyett J, Jauniaux E. Obstetric outcome after threatened
miscarriage with and without a hematoma on ultrasound. Obstet Gynecol
2003;102:483-7.
Everett C, Ashurst H, Chalmers I. Reported management of threatened
miscarriage by general practitioners in Wessex. BMJ 1987;295:583-6.
Falco P, Milano V, Pilu G, David C, Grisolia G, Rizzo N, Bovicelli L.
Sonography of pregnancies with first-trimester bleeding and a viable
embryo: a study of prognostic indicators by logistic regression analysis.
Ultrasound Obstet Gynecol 1996;7:165-9.
Falco P, Zagonari S, Gabrielli S, Bevini M, Pilu G, Bovicelli L. Sonography
of pregnancies with first-trimester bleeding and a small intrauterine gestational sac without a demonstrable embryo. Ultrasound Obstet Gynecol
2003;21:62-5.
Tongsong T, Wanapirak C, Srisomboon J, Sirichotiyakul S, Polsrisuthikul
T, Pongsatha S. Transvaginal ultrasound in threatened abortions with
empty gestational sacs. Int J Gynaecol Obstet 1994;46:297-301.
Tongsong T, Srisomboon J, Wanapirak C, Sirichotiyakul S, Pongsatha S,
Polsrisuthikul T. Pregnancy outcome of threatened abortion with
demonstrable fetal cardiac activity: a cohort study. J Obstet Gynaecol
1995;21:331-5.
Tannirandorn Y, Sangsawang S, Manotaya S, Uerpairojkit B, Samritpradit
P, Charoenvidhya D. Fetal loss in threatened abortion after embryonic/
fetal heart activity. Int J Gynaecol Obstet 2003;81:263-6.
Everett CB, Preece E. Women with bleeding in the first 20 weeks of pregnancy: value of general practice ultrasound in detecting fetal heart movement. Br J Gen Pract 1996;46:7-9.
La Marca A, Morgante G, De Leo V. Human chorionic gonadotrophin,
thyroid function, and immunological indices in threatened abortion.
Obstet Gynecol 1998;92:206-11.
al-Sebai MA, Diver M, Hipkin LJ. The role of a single free beta-human
chorionic gonadotrophin measurement in the diagnosis of early
pregnancy failure and the prognosis of fetal viability. Hum Reprod
1996;11:881-8.
Reljic M. The significance of crown-rump length measurement for
predicting adverse pregnancy outcome of threatened abortion.
Ultrasound Obstet Gynecol 2001;17:510-2.
Bennett GL, Bromley B, Lieberman E, Benacerraf BR. Subchorionic
hemorrhage in first-trimester pregnancies: prediction of pregnancy outcome with sonography. Radiology 1996;200:803-6.
Pedersen JF, Mantoni M. Prevalence and significance of subchorionic
hemorrhage in threatened abortion: a sonographic study. Am J Roentgenol
1990;154:535-7.
Dickey RP, Olar TT, Curole DN, Taylor SN, Matulich EM. Relationship of
first-trimester subchorionic bleeding detected by color Doppler
ultrasound to subchorionic fluid, clinical bleeding, and pregnancy
outcome. Obstet Gynecol 1992;80:415-20.
Nagy S, Bush M, Stone J, Lapinski RH, Gardo S. Clinical significance of
subchorionic and retroplacental hematomas detected in the first trimester of pregnancy. Obstet Gynecol 2003;102:94-100.
al-Sebai MA, Kingsland CR, Diver M, Hipkin L, McFadyen IR. The role of
a single progesterone measurement in the diagnosis of early pregnancy
failure and the prognosis of fetal viability. Br J Obstet Gynaecol
1995;102:364-9.
Florio P, Luisi S, DAntona D, Severi FM, Rago G, Petraglia F. Maternal
serum inhibin A levels may predict pregnancy outcome in women with
threatened abortion. Fertil Steril 2004;81:468-70.
Schmidt T, Rein DT, Foth D, Eibach HW, Kurbacher CM, Mallmann P, et
al. Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy. Eur J Obstet Gynecol Reprod Biol 2001;97:168-73.
Fiegler P, Katz M, Kaminski K, Rudol G. Clinical value of a single serum
CA-125 level in women with symptoms of imminent abortion during the
first trimester of pregnancy. J Reprod Med 2003;48:982-8.
Ruge S, Pedersen JF, Sorensen S, Lange AP. Can pregnancy-associated
plasma protein A (PAPP-A) predict the outcome of pregnancy in women
with threatened abortion and confirmed fetal viability? Acta Obstet Gynecol Scand 1990;69:589-95.
Harrison RF. A comparative study of human chorionic gonadotropin,
placebo, and bed rest for women with early threatened abortion. Int J Fertil Menopausal Stud 1993;38:160-5.
Giobbe M, Fazzio M, Boni T. [Current role of bed-rest in threatened abortion]. Minerva Ginecol 2001;53:337-40.
Ben-Haroush A, Yogev Y, Mashiach R, Meizner I. Pregnancy outcome of
threatened abortion with subchorionic hematoma: possible benefit of
bed-rest? Isr Med Assoc J 2003;5:422-4.
Oates-Whitehead RM, Haas DM, Carrier JAK. Progestogen for
preventing miscarriage. In: Cochrane Library. Chichester: Wiley, 2003.
(Issue 4.)
155